crossing96/oncoscreening huggingface dataset:
Genetic risk scores based on risk-associated single nucleotide polymorphisms can reveal inherited risk of bladder cancer in Chinese population.	Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with bladder cancer (BCa) risk in Caucasian and East Asian population. The objective of this study was to validate these SNPs in Chinese population and evaluate whether these SNPs could differentiate the individual inherited risk for BCa.A case-control study including 581 BCa cases and 1561 healthy controls was performed. Germline DNA samples from all individuals were genotyped for eight SNPs. Genetic risk score (GRS) was calculated for each individual based on the odds ratios and risk allele frequencies of five risk-associated SNPs.Among eight SNPs evaluated in this study, rs798766 at 4p16.3 [OR = 1.39 (1.15-1.67), P < .001], rs9642880 [OR = 1.17 (1.06-1.30), P < .001] and rs4813953 at 20p12.2 [OR = 1.09 (1.02-1.17), P = .016] were found associated with BCa risk in Chinese population. A genetic risk score was established based on five SNPs (including the above three SNPs and two other SNPs which have the consistent direction with previous reported genome-wide association study). The mean GRS was significantly higher in BCa cases than controls (1.22 vs. 1.01, P < .001). When subjects were categorized into low- (<0.8), average- (0.8-1.2), and high-risk (>1.2) groups, the likelihoods of BCa were 25.2%, 33.7% and 55.0%, respectively (P-trend < 2.2 × 10). In subgroup analyses, no significant difference was observed in mean GRS among BCa patients with different stages or grades.In conclusion, two SNPs derived from East Asian and one SNP from Caucasian were associated with BCa risk in Chinese population. These results provided additional information of genetic risks for BCa in Chinese population. Genetic risk score based on these SNPs can reveal inherited risk of BCa, and may have potential for modifying personalized cancer screening strategy.	bladder
UNC5B mediates G2/M phase arrest of bladder cancer cells by binding to CDC14A and P53.	UNC5B is a known tumor suppressor gene in a variety of cancers. As a transmembrane protein, UNC5B also induces apoptosis in a P53-dependent manner. In this study, we demonstrate that UNC5B inhibits proliferation through G2/M phase arrest by mass spectrometry and bioinformatics analysis in bladder cancer cells. By combing with CDC14A and P53, UNC5B dephosphorylated P53 at Ser-315 site. This dephosphorylation facilitated G2/M phase arrest by reducing the expression of cyclin B1 and increasing the expression of p-CDK1, thus inhibiting tumor proliferation. Knockdown of CDC14A suppressed the G2/M phase arrest induced by UNC5B in vitro, and eliminated the inhibitory effect of UNC5B on tumor proliferation in vivo. Our results show that UNC5B-mediated cell cycle arrest may act as a potential treatment for bladder cancer.	bladder
CircRNA 001418 Promoted Cell Growth and Metastasis of Bladder Carcinoma via EphA2 by miR-1297.	BACKGROUND: Cancer is one of the major causes of human deaths at present. It is the leading cause of deaths in developed countries. Moreover, Circular RNAs (circRNAs) have been discovered to play important roles in tumor genesis and development and are abnormally expressed in bladder cancer . OBJECTIVE: The present study aims to investigate the anti-cancer effects of circ 001418 on bladder carcinoma and its possible mechanism. METHODS: Quantitative PCR (qPCR) and gene chip were used to measure the circ 001418 expression. Cell proliferation and transfer, apoptosis and caspase-8 and caspase-3 activity levels were measured using MTT, Transwell assay, Flow cytometry. Caspase-3 and 9 activity levels, EphA2, cytochrome c and FADD protein expression, were detected using Western blotting. RESULTS: The expression of circ 001418 was increased in patients with bladder carcinoma. Over-expression of circ 001418 promoted cell proliferation and transfer, and reduced apoptosis in vitro model of bladder carcinoma. Down-regulation of Circ 001418 inhibited cell proliferation and transfer, and induced apoptosis in vitro model of bladder carcinoma. Meanwhile, over-expression of circ 001418 induced EphA2 and cytochrome c protein expression, and suppressed FADD protein expression in vitro model of bladder carcinoma by the suppression of miR-1297. MiR-1297 reduced the pro-cancer effect of circ 001418 on apoptosis of bladder carcinoma. CONCLUSION: Results showed that circRNA 001418 promoted cell growth and metastasis of bladder carcinoma via EphA2 by miR-1297.	bladder
Long non-coding RNA LINC00675 is associated with bladder cancer metastasis and patient survival.	BACKGROUND: Muscle-invasive bladder cancer (MIBC), a bladder cancer that spreads into the detrusor muscle of the bladder, leads to a poor outcome. Long noncoding RNA LINC00675 has been reported to play import roles in several cancer types, although its biological function and underlying mechanism in MIBC remain largely unclear. METHODS: Eighty-nine patients with MIBC were enrolled in the present study. RNA expression was measured using a quantitative reverse transcription-polymerase chain reaction. Protein expression was detected using western blotting. Transwell assays were performed to analyze the abilities of bladder cancer cells to migrate and invade. An RNA microarray was carried out to analyze LINC00675-regulated mRNAs in bladder cancer cells. RESULTS: We found that LINC00675 expression was decreased in MIBC tissues compared to matched normal tissues, and was correlated with lymph node-metastatic MIBC. MIBC patients with low expression of LINC00675 had worse survival rates than those with high expression. Functional investigation showed that ectopic expression of LINC00675 inhibited bladder cancer cell migration, invasion and proliferation, whereas LINC00675 knockdown presented an opposite effect. Mechanistically, we found that LINC00675 inhibited β-catenin and its downstream gene expression. CONCLUSIONS: The findings of the present study suggest that LINC00675 regulates β-catenin expression, and is associated with bladder cancer metastasis and patient survival.	bladder
Whole-bladder Radiation Therapy for Lymph Node-negative Bladder Cancer With Muscle Invasion in Elderly Patients.	BACKGROUND: The Japanese bladder cancer treatment guidelines recommend concurrent chemoradiotherapy, including wide pelvic irradiation. Many elderly patients, however, cannot tolerate standard treatment because of low performance status. Therefore, to reduce complications, elderly patients sometimes receive radiation therapy without elective nodal irradiation or chemotherapy. PATIENTS AND METHODS: Outcomes were retrospectively analyzed in 19 elderly patients with N0 muscle-invasive bladder cancer treated with whole-bladder irradiation without chemotherapy. RESULTS: The 3- and 5-year overall survival rates were 30.7% and 12.2%, respectively. No patient experienced severe late complications (grade 3 or higher). Recurrence was observed in 11 patients (57.9%). The initial location of recurrence was within the bladder. CONCLUSION: Whole-bladder irradiation alone did not increase lymph node metastases or severe complications in elderly patients. Whole-bladder radiation therapy without chemotherapy or wide pelvic irradiation may be a promising treatment method for patients who are not candidates for standardized treatment.	bladder
Relapse and Prognosis of Non-Muscle Invasive Bladder Cancer After Combined HOLRBT with Sunitinib and TGC Perfusion Chemotherapy.	Objective: To prevent postoperative relapse after HOLRBT, we compared postoperative adjuvant therapies. Methods: One hundred fifty patients with non-muscle invasive bladder cancer (NMIBC) were meanly divided into three groups: A, B, and C. Group A patients only took sunitinib, group B patients underwent TGC perfusion chemotherapy, and group C patients took sunitinib and underwent TGC chemotherapy. Results: It was discovered that TGC perfusion chemotherapy combined with taking sunitinib can significantly reduce the relapse rate. Most of the tumor relapse period was assembled at 9 months after the operation. No-tumor relapse survival rate and no-fluorescence in situ hybridization positive survival rate in Group C were significantly higher than those of Group A and Group B. Conclusion: Therefore, the combined application of taking sunitinib drug and going through TGC perfusion chemotherapy after secondary HOLRBT will evidently improve the prognosis of patients with a glorious applicated prospect.	bladder
Clinical value of texture analysis in differentiation of urothelial carcinoma based on multiphase computed tomography images.	Identification of histologic grading of urothelial carcinoma still depends on histopathologic examination. As an emerging and promising imaging technology, radiomic texture analysis is a noninvasive technique and has been studied to differentiate various tumors. This study explored the value of computed tomography (CT) texture analysis for the differentiation of low-grade urothelial carcinoma (LGUC), high-grade urothelial carcinoma (HGUC), and their invasive properties.Radiologic data were analyzed retrospectively for 94 patients with pathologically proven urothelial carcinomas from November 2016 to April 2019. Pathologic examination demonstrated that tumors were: high grade in 43 cases, and low grade in 51 cases; and nonmuscle invasive (NMI) in 37 cases, and muscle invasive (MI) in 37 cases. Maximum tumor diameters on CT scan were manually outlined as regions of interest and 78 texture features were extracted automatically. Three-phasic CT images were used to measure texture parameters, which were compared with postoperative pathologic grading and invasive results. The independent sample t test or Mann-Whitney U test was used to compare differences in parameters. Receiver-operating characteristic curves for statistically significant parameters were used to confirm efficacy.Of the 78 features extracted from each phase of CT images, 26 (33%), 20 (26%), and 22 (28%) texture parameters were significant (P < .05) for differentiating LGUC from HGUC, while 19 (24%), 16 (21%), and 30 (38%) were significant (P < .05) for differentiating NMI from MI urothelial carcinoma. Highest areas the under curve for differentiating grading and invasive properties were obtained by variance (0.761, P < .001) and correlation (0.798, P < .001) on venous-phase CT images.Texture analysis has the potential to distinguish LGUC and HGUC, or NMI from MI urothelial carcinoma, before surgery.	bladder
Integrin β8 facilitates tumor growth and drug resistance through a Y-box binding protein 1-dependent signaling pathway in bladder cancer.	The transmembrane receptors integrins are the bridges for cell-cell or cell-ECM interaction, which is strictly correlated to cancer development in several tumor types. Here, we revealed that integrin β8 serves as a driver to mediate sustained growth of bladder cancer and development of drug resistance. The elevated expression of integrin β8 was observed in highly malignant bladder tumor tissues from patients. The in vitro and in vivo results further indicated that integrin β8 overexpression in Biu87/T24 bladder cancer could mediate and strengthen cell proliferation and resistance to mitomycin C and hydroxycamptothecin. Mechanistically, integrin β8 on the cellular surface might recruit phosphorylated Y-box binding protein 1, leading to the activation of c-Myc and nuclear factor-κB signals. Pharmacological targeting of integrin β8 by Arg-Gly-Asp-Ser efficiently suppressed sustained growth and drug resistance in bladder cancer cells. Our findings identified integrin β8 as a marker of bladder cancer diagnosis and development, and provides an innovative approach for clinical bladder cancer therapy.	bladder
Sex-specific Alterations in the Urinary and Tissue Microbiome in Therapy-naïve Urothelial Bladder Cancer Patients.	Comprehensive characterization of the urinary and urothelium-bound microbiomes in bladder cancer (BCa) and healthy state is essential to understand how these local microbiomes may play a role in BCa tumorigenesis and response to therapy, as well as to explain sex-based differences in BCa pathobiology. Performing 16 s rDNA microbiome analysis on 166 samples (urine and paired bladder tissues) from therapy-naïve BCa patients undergoing radical cystectomy and healthy controls, we defined (1) sex-specific microbiome differences in the urine and bladder tissue, and (2) representativeness of the tissue microenvironment by the voided urinary microbiome. The genus Klebsiella was more common in the urine of female BCa patients versus healthy controls, while no clinically relevant bacteria were found differently enriched in men. In tissues, the genus Burkholderia was more abundant in the neoplastic versus the non-neoplastic tissue in both sexes, suggesting a potential role in BCa pathobiology. Lastly, we found that the urinary microbiome shares >80% of the bacterial families present in the paired bladder tissue, making the urinary microbiome a fair proxy of the tissue bacterial environment. PATIENT SUMMARY: We identified specific bacteria present in the urine and tissues of male and female bladder cancer patients. These novel data represent a first step toward understanding the influence of the bladder microbiome on the development of bladder cancer and on the response to intravesical and systemic therapies.	bladder
Novel o-Toluidine Metabolite in Rat Urine Associated with Urinary Bladder Carcinogenesis.	o-Toluidine (o-Tol), a monocyclic aromatic amine, causes bladder cancer in humans and experimental animals and is therefore classified as a Group 1 carcinogen (IARC) in which the carcinogenicity of o-Tol is involved in metabolic activation, DNA damage, and DNA adduct formation. In the DNA adduct formation mechanism, o-Tol is metabolized by N-hydroxylation, N-acetoxylation, and then deacetoxylation to produce an electrophilic nitrenium ion, which is able to bind to a DNA base, such as dG-C8. Therefore, dG-C8-o-Tol is thought to be a plausible DNA adduct of o-Tol exposure. However, direct detection of dG-C8-o-Tol in biological samples has not been reported yet. Here, we show that a novel o-Tol metabolite, 2-methyl-N(1)-(2-methylphenyl)benzene-1,4-diamine (MMBD), a dimer by head-to-tail binding, was identified for the first time in o-Tol-exposed rat urine. MMBD was also detected in a reaction of o-Tol and S9 mix, indicating the formation was catalyzed by an enzymatic reaction. Moreover, MMBD showed a potent stronger mutagenicity in N-acetyltransferase overexpressed Salmonella typhimurium strains,and cytotoxicity in human bladder carcinoma T24 cells and human spleen lymphoblastoid TK6 cells compared with o-Tol. Furthermore, a DNA adduct (m/z 478.1) corresponding to dG-MMBD was detected in the reaction of calf thymus DNA with rat urine containing MMBD, and also in hepatic DNA of rats treated with o-Tol. These results therefore suggested that o-Tol-induced bladder carcinogenesis could be at least partly attributed to MMBD formation. The possible dimerization of monocyclic aromatic amines should be considered in the evaluation of the risk of bladder carcinogenesis after exposure.	bladder
Trp53 Mutation in Keratin 5 (Krt5)-Expressing Basal Cells Facilitates the Development of Basal Squamous-Like Invasive Bladder Cancer in the Chemical Carcinogenesis of Mouse Bladder.	The biological processes of urothelial carcinogenesis are not fully understood, particularly regarding the relationship between specific genetic events, cell of origin, and molecular subtypes of subsequent tumors. N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced mouse bladder cancer is widely accepted as a useful model that recapitulates the pathway of human bladder tumorigenesis from dysplasia to invasive cancer via carcinoma in situ. However, the long and variable time of tumorigenesis often hinders efficient preclinical or translational research. We hypothesized that Trp53 mutation in specific types of urothelial cells facilitates efficient development of clinically relevant bladder cancer. Using lineage tracing, we showed that Trp53 mutation in Krt5-expressing cells resulted in more efficient tumorigenesis of mouse muscle-invasive bladder cancer (MIBC) with squamous differentiation compared with Trp53 mutation in Upk2-expressing cells, or wild-type or hemizygous Trp53 in the entire urothelium. Mouse MIBC that developed at 24 weeks of BBN treatment showed morphologic and genetic similarities to the basal squamous subtypes of human MIBC, irrespective of pre-induction of Trp53 mutation or whether the cell of origin was Krt5- or Upk2-expressing cells. Our findings suggest that intermediate cells as well as basal cells also can give rise to basal-like MIBC, with pre-induction of Trp53 mutation accelerating MIBC. Thus, in BBN chemical carcinogenesis, pre-induction of Trp53 mutation in basal cells facilitates efficient modeling of the basal squamous subtype of human MIBC.	bladder
An affinity chromatography and glycoproteomics workflow to profile the chondroitin sulfate proteoglycans that interact with malarial VAR2CSA in the placenta and in cancer.	Chondroitin sulfate (CS) is the placental receptor for the VAR2CSA malaria protein, expressed at the surface of infected erythrocytes during Plasmodium falciparum infection. Infected cells adhere to syncytiotrophoblasts or get trapped within the intervillous space by binding to a determinant in a 4-O-sulfated CS chains. However, the exact structure of these glycan sequences remains unclear. VAR2CSA-reactive CS is also expressed by tumor cells, making it an attractive target for cancer diagnosis and therapeutics. The identities of the proteoglycans carrying these modifications in placental and cancer tissues remain poorly characterized. This information is clinically relevant since presentation of the glycan chains may be mediated by novel core proteins or by a limited subset of established proteoglycans. To address this question, VAR2CSA-binding proteoglycans were affinity-purified from the human placenta, tumor tissues and cancer cells and analyzed through a specialized glycoproteomics workflow. We show that VAR2CSA-reactive CS chains associate with a heterogenous group of proteoglycans, including novel core proteins. Additionally, this work demonstrates how affinity purification in combination with glycoproteomics analysis can facilitate the characterization of CSPGs with distinct CS epitopes. A similar workflow can be applied to investigate the interaction of CSPGs with other CS binding lectins as well.	bladder
Molecular subtyping bladder cancer: Is it ready for clinical practice?	Bladder cancer, one of the more common cancers, is a heterogeneous disease, both morphologically and clinically. Although histological classification and extent of the disease (staging) guide treatment options, the heterogeneity in responses to therapy highlights the need for better stratification of patients for the appropriate therapy in order to achieve better outcomes. Several molecular classifications of muscle-invasive bladder cancer have been proposed but currently their use in clinical practice is limited by the complexity of the methods used and diversity of the subtypes.	bladder
Recurrent Bladder Cancer in a Teenage Male.	Urothelial cell carcinoma of the bladder is exceedingly rare in pediatric patients. Based on current literature, bladder cancer in this population is thought to be low-grade, noninvasive, and unlikely to recur, suggesting significant biologic differences when compared to the adult population. This is a 15-year-old male diagnosed with low-grade urothelial cell carcinoma with subsequent multifocal recurrence on surveillance cystoscopy managed by induction and maintenance intravesical Bacillus Calmette-Guerin. This case highlights the challenges of management and surveillance of this rare disease.	bladder
Antibiotic prophylaxis in transurethral resection of bladder tumours: study protocol for a systematic review and meta-analysis.	BACKGROUND: The necessity of antibiotic prophylaxis for postoperative urinary tract infections (UTIs) after transurethral resection of bladder tumours is controversial. This potentially leads to the overuse of antibiotic prophylaxis and rising antimicrobial resistance rates. The objective of this systematic review and meta-analysis is to compare the impact of different antimicrobial prophylaxis schemes versus placebo on the prevention of postoperative UTI and asymptomatic bacteriuria. METHODS: We designed and registered a study protocol for a systematic review and meta-analysis of randomized controlled trials and non-randomized (e.g. cohort, case-control) studies examining any form of antibiotic prophylaxis in patients with transurethral resection of bladder tumours. Literature searches will be conducted in several electronic databases (from inception onwards), including MEDLINE (Ovid), EMBASE (Ovid), and the Cochrane Central Register of Controlled Trials (CENTRAL). Grey literature will be identified through searching conference abstracts. The primary outcome will be postoperative urinary tract infections. The secondary outcome will be asymptomatic bacteriuria. Two reviewers will independently screen all citations, full-text articles, and abstract data. Potential conflicts will be resolved through discussion. The study methodological quality (or bias) will be appraised using appropriate tools (e.g. Risk of Bias 2.0 tool and Newcastle-Ottawa Scale). If feasible, we will conduct random-effects meta-analysis of outcome data. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g. study design, publication year, the setting of the study, and antibiotics regimen). We will also search, identify, and discuss potential risk factors for urinary tract infections following transurethral resection of bladder tumours. This may serve as basis for a scoping review. DISCUSSION: In times of rising antimicrobial resistance rates, sound evidence on the necessity of antibiotic prophylaxis is essential for implementation into guideline recommendations and for decision-making in clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019131733.	bladder
Mitigation of aflatoxin B1- and sodium arsenite-induced cytotoxicities in HUC-PC urinary bladder cells by curcumin and Khaya senegalensis.	Background Concomitant exposure to environmental/occupational toxicants such as aflatoxin B1 (AFB1) and arsenic in some regions of the world has been well reported. Therefore, this calls for the assessment of the efficacy of agents such as phytochemicals, which are already known for their ethno-medicinal uses in prophylaxis/remediation. We investigated the possible cytotoxic bio-interactions between AFB1 and sodium arsenite (SA) in urinary bladder cells. We also assessed the cytoprotective effects of curcumin and the ethanol stem bark extract of Khaya senegalensis (K2S). Methods The cells were exposed to graded levels of AFB1, SA, curcumin, and K2S for 24, 48, and 72 h. Subsequently, using optimum toxic concentrations of AFB1 and SA, respectively, the influence of non-toxic levels of curcumin and/or K2S was tested on exposure of the cells to AFB1 and/or SA. Hoechst 33342/propidium iodide staining technique was used to determine the end-points due to cytotoxicity with changes in adenosine triphosphate (ATP) levels determined using Promega's CellTiter-Glo luminescent assay. Results Co-treatment of the cells with AFB1 and SA resulted in synergy in cytotoxic effects. Cytotoxicity was reduced by 3.5- and 2.9-fold by pre-treatment of the cells with curcumin and K2S before treatment with AFB1, while post-treatment resulted in 1.1- and 2.6-fold reduction, respectively. Pre-exposure of the cells with curcumin and K2S before treatment with SA ameliorated cytotoxicity by 3.8- and 3.0-fold, but post-treatment caused a 1.2- and 1.3-fold reduction, respectively. Conclusions Pre-treatment of the cells with either curcumin or K2S exhibited cytoprotective effects by ameliorating AFB1- and SA-induced cytotoxicity with inferred tendencies to prevent carcinogenesis.	bladder